The long-term goal of this research program continues: to evaluate myocardial function and physiology with high temporal and spatial resolution using advanced multidimensional ultrasound methods. The specific goals of this proposed project for the next five years are: 1) to relate localized in-plane wall stress, to the vibroacoustography signal in excised perfused slabs of myocardium and later, in open chest pigs, 2) to relate local myocardial in-plane strain, measured with tissue Doppler gradients from our intra-cardiac ultrasound catheter, to vibro-acoustography signals, 3) to measure myocardial perfusion (ml gram-1 min about') from contrast bubble concentration, with vibro-acoustography using high ultrasound intensity to clear out bubbles, and then 4) to apply these methods to characterizing localized myocardial conditions of normal, ischemia, infarct, and reperfusion, in the hearts of open chest pigs validated with gross vital staining and histology. These specific goals will be accomplished with two new imaging methods, both recently developed at Mayo Clinic. The first is an intracardiac ultrasound imaging catheter developed in collaboration between the Mayo echocardiography group and Acuson Corporation (AcuNav, Acuson, Inc., Mountain View, CA). The intracardiac catheter (ICE) can measure tissue myocardial Doppler velocity gradients, which are a rough estimate of strain rate along the direction of the ultrasound beam. The second recently developed imaging method is "vibro-acoustographic emission" or VAE. VAE uses radiation force induced vibration of myocardium, detected with a hydrophone, to estimate stiffness with high spatial and temporal resolution (-0.7cc, 200 samples/second, respectively). In controlled in vitro and in vivo studies we will validate the ability of VAE to estimate wall stress from measurements of stiffness and of ICE to estimate strain. We also propose that VAE can assess inflow rates of contrast microbubbles, and thus provide an estimate of blood perfusion, within localized (-0.7cc) regions in the myocardium. When VAE, validated in this program, is combined with the ICE catheter in a future clinical instrument, highly localized stress, strain and perfusion could be estimated within the mvocardium.